Introduction: Multiple sclerosis (MS) is a long-term autoimmune condition linked to inflammation mediated by the central nervous system. The immune system targets the myelin sheath that surrounds nerve fibers in multiple sclerosis, which impairs brain-to-body communication. One of the main pathological characteristics of MS that affect the brain and have a variety of consequences on nerve impulse conduction is inflammation and demyelination of spinal nerve cells. Zone foot reflexology massage is the most popular kind of reflexology, sometimes referred to as foot reflexology or reflexology massage. It is founded on the idea that particular regions on the soles of the feet represent various bodily parts and functions. MS symptomatic management plays acrucial role in improving a patient's QoL on a daily basis; however, it is important to understand that symptomatic management does not alter the course of the disease; rather, it focuses on specific symptoms, offering relief and improving functionality. Complementary interventions alongside constant therapy are often still essential to MS management, allowing patients to effectively control their symptoms and maintain their overall QoL. So, these interventions should be implemented for MS patients to achieve a positive health outcome by preventing consequences from the disease's progression and negative drug effects . Aim of the study: The aim of the study was to evaluate the responsiveness of pain and fatigue of patients with multiple sclerosis to the Zone foot reflexology massage through: - Assessing the baseline levels of pain and fatigue in patients with multiple sclerosis. - Designing and implementing zone foot reflexology massage sessions on the patients with multiple sclerosis who are suffering from pain and fatigue. - Evaluating the effect of zone foot reflexology massage on the pain and fatigue levels of patients with multiple sclerosis Hypothesis This study achieved the following hypothesis: - H1: The pain level in study group patients will respond positively and decrease after Zone foot reflexology massage sessions intervention compared to control group patients. - H2: The fatigue level in study group patients will respond positively and decrease after Zone foot reflexology massage sessions intervention compared to control group patients. 1 Research Design: A quasi-experimental two-group research design with pre- and post- tests (repeated measurements) on the study and control groups was utilized to conduct the study. Study setting: The study was conducted in the Multiple Sclerosis (MS) clinic belonging to the neurological diseases outpatient clinic at Zagazig University Hospitals, Al Sharqia Governorate, Egypt. The MS clinic present on the second floor of the outpatient clinics building at Zagazig University Hospitals comprises an examination room. Study Sample: A purposive sample of 60 MS patients who are being treated or monitored in the aforementioned location; the following were requirements for inclusion: being at least eighteen years old, both male and female, having been diagnosed with MS at least six months prior, being able to walk without assistance, experiencing pain and fatigue, not having visual or hearing impairment, not having previously used complementary and alternative therapies, having both right and left feet, not having vascular disease, ulcers, infections, fractures, sprains, or surgical procedures in either foot and not being pregnant. Tools for data collection: Tool I: A structured interview questionnaire: It to assess the patients' demographic and medical history. It had the following two parts: - Part 1: Socio-demographic characteristics: Five items concerning the patient's age, gender, degree of education, marital status, and occupation were included in this part. Part 2: Medical history information: This part was used to evaluate the patient's medical history; it included information on the type of MS, neurological symptoms, and drug use status. Tool II: The Visual Analog Scale (VAS): It was created by Bond & Pilowsky (1966) and is used to convert numerical values that are not quantitatively measurable. The researchers adopted it to assess the pain level of the studied patients. Tool III: The Fatigue Severity Scale (FSS): The FSS is adopted from Krupp et al., (1989) to evaluate the degree and effect of fatigue, especially in MS patients. The scale addresses fatigue’s effects on daily functioning, querying its relationship to motivation, physical activity, work, family, and social life, and asking respondents to rate the ease with which they are fatigued and the degree to which the symptom poses a problem for them. Pilot study: The clarity, relevance, comprehensiveness, comprehension, applicability, and ease of use of the tool were assessed on six patients or 10% of the primary study sample. It also aided in calculating the time needed to do the paperwork(tools). Patients who participated in the pilot study were included in the actual study population because the instruments had not been changed. Field work The current study was carried out in the following order: A- Preparatory stage (Assessment stage): - Data for this study was gathered over a six- month period, from early April 2024 to September 2024. The dean of Zagazig University's nursing faculty and the director of Zagazig University hospitals provided the researchers with the required formal approval before the study was conducted during the assessment phase. B. Planning stage: - The researcher created the program's goals; priorities, contents, and expected outcomes based on the information gathered during the assessment phase and the 1 examination of relevant literature, taking into account the requirements and issues of the patients. To ensure that all patients are educated and involved to promote their cooperation during the intervention, the researcher also created a booklet about MS disease and Zone foot reflexology massage, which was given to every patient in the study group throughout the implementation stage and given to control group patients at the end of the study. C. Implementation stage: Regard to patients in the control group had their usual routine treatment or care and received no intervention. While study group patients had two sessions of Zone foot reflexology massage weekly for a total of twelve weeks in addition to their usual routine treatment or care. Also, prior to beginningZonefoot reflexology massage sessions, theresearchers designed a 30- to 40-minutebasichealth education session for the studygrouppatients. Evaluation stage: - After 8 and 12 weeks of Zone foot reflexology massage application to the study group and after standard treatment or care for the control group, the same data collection tools (Tool II &Tool III) used at the pre-test were used post-test for both groups in order to assess the responsiveness of MS patients' pain and fatigue to the Zone foot reflexology massage, which reflects its efficacy in reducing both complaints. Results: A statistically significant difference and decrease were observed in pain mean scores (p = 0.005 & 0.001) and fatigue mean scores (p = 0.004 & 0.001) of study group patients compared to the control group post-8 th and 12 th week, respectively, of Zone foot reflexology massage intervention. Conclusion: It can be concluded that the pain and fatigue of patients with MS respond positively to Zone foot reflexology massage sessions, which reflects the significant effect of Zone foot reflexology massage in decreasing and improving the pain and fatigue of those patients. This is evidenced by the presence of a statistically significant difference and decrease in the mean scores of pain and fatigue level in study group patients compared to the control group in the post intervention phase of Zone foot reflexology massage, also between the pre-and post intervention phase of it. Recommendation: 1. Zone foot reflexology massage should be a key component of provided care for patients with MS in addition to pharmacological treatments or used as a part of early strategies for controlling the pain and fatigue symptoms of those patients. 2. Developing and implementing a training program for nurses and other healthcare professionals in Zone foot reflexology massage may aid in recognizing it as an essential part of routine care procedures. 3. In order to enable a broader generalization of the results, the study should be replicated with a larger sample size and a longer duration of exposure to Zone foot reflexology massage.