Background: Glypican-4 (GPC4) is a novel adipokine thataffects insulin signaling, and adipocyte differentiation. Serum GPC4 level was associatedwith obesity-related param-eters such as hyperglycaemia, Insulin Resistance (IR), and elevated liver enzymes aspartate Amino-Transferase (AST), and alanine Amino-Transferase (ALT). Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as one of the manifestations of metabolic syndrome. It is usually associated with IR, dyslipidemia, and elevated AST & ALT levels. Few studies were performed to elucidate the role of GPC4 in the development of NAFLD in human, and its relation to other metabolic parameters. But, its exact role hasn't been clarified yet. Aim of Study: To estimate serum level of GPC4 in NAFLD induced by high fat diet in adult male albino rats, and to examine its relationship to other metabolic parameters. Material and Methods: A total number of 60 healthy adult male local strain albino rats were divided into 2 main groups: Control group (I) (n=30) were fed on standard chow, and was further subdivided according to the period of their nourishment on standard chowinto 3 equal subgroups (n=10), subgroup (IA), for 4 weeks, subgroup (IB), for 12 weeks, andsubgroup (IC), for 24 weeks High Fat Diet (HFD) fed group (II) (n=30) were fed on high fat chow, and was further subdivided accord-ing to the period of their nourishment on HFDinto 3 equal subgroups (n=10), subgroup (IIA): For 4 weeks, subgroup (IIB), for 12 weeks, andsubgroup (IIC), for 24 weeks. Body Mass Index (BMI), Abdominal Circumference (AC) were measured. Serum GPC4, glucose, insulin, ofhomeostasis model assessment (HOMA-IR)-index, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), AST, ALT, and C-Reactive Protein (CRP) were estimated. Liver histopathology was studied. Results: GPC4 was positively correlated with BMI, AC, TC, TG, LDL, AST, ALT, and CRP in all HFD-fed rats groups. Concerning, IR and HOMA-IR, it was found that, GPC4 was positively correlated with both of them in HFD-fed rats for4 weeks and 12 weeks groups, however, no correlations were reported between GPC4 and IR & HOMA-IR in HFD-fed rats for 24 weeks group. Conclusion: Serum GPC4 level was increased in HFD-fed rats for 4 weeks and 12 weeks groups as a compensatory mechanism to overcome IR, and was reduced in HFD-fed rats for 24 weeks group due to failure of compensation as a result of marked progress of IR.