Objective: This study was designed to investigate the effect of Phyllanthus reticulatus on lipid profile and oxidative stress in hypercholesterolemic albino rats. Materials and Methods: Hypercholesterolemia was induced in albino rats by administration of atherogenic diet for 2 weeks. Experimental rats were divided into different groups: normal, hypercholesterolemic control and P. reticulatus treated (250 and 500 mg/kg body weight doses for 45 days). After the treatment period of 45 th day triglyceride, VLDL-cholesterol, HDL-cholesterol, total cholesterol (TC), LDL-cholesterol and oxidative stress (protein carbonyl) were assayed and compared with hypercholesterolemic control. Results: The aqueous extract of P. reticulatus (250 mg and 500 mg/kg) produced significant reduction (P < 0.05) in triglyceride, VLDL-cholesterol, total cholesterol (TC), LDL-cholesterol and oxidative stress (protein carbonyl) while increased HDL-cholesterol in atherogenic diet-induced hypercholesterolemic rats at the end of the treatment period (45 days). However, the reduction in the above parameters was comparable with hypercholesterolemic control. Thus, aqueous extract of P. reticulatus is effective in controlling TC, lipid profile and oxidative stress in hypercholesterolemic animals. Conclusion: The results suggest the aqueous extract of P. reticulatus can be utilized for prevention of atherosclerosis in hypercholesterolemic patients.