Background: Multiple sclerosis (MS) is a chronic disease with a wide range of pathologic changes that modify the apparent diffusion coefficient (ADC) value. Patients & methods: A prospective study included Forty two MS patients, underwent conventional and diffusion weighted MR imaging with ADC measurement in plaques and normally appearing white matter (NAWM), compared with normal white matter (NWM) of a control group (n=21). They were followed-up six months later. Results: Significantly higher ADC values were found in acute and secondary progressive cases than relapsing remitting (RR) cases and all values were higher than in normal white matter. A higher ADC values was found in NAWM than control cases and in the newly developed plaques relative to old plaques in all types. A cut off ADC value 1.02 ± 0.20×10−3mm2/sec was detected for MS diagnosis, a value 1.41 ± 0.10×10−3mm2/sec to separate between acute and chronic RR cases and 1.2 ± 0.10×10−3mm2/sec to differentiate chronic subtypes. Conclusion: ADC value has the validity in diagnosis and follow-up of MS patients with different clinical subtypes.