Abstract: Based on the high-fat diet of successfully modeled obese and hypercholesterolemic rats, using simvastatin as a positive control, the results of epigallocatechin gallate (EGCG, 83.3 mg·kg⁻¹·d⁻¹) + L-Theanine (16.7 mg·kg⁻¹·d⁻¹), EGCG (100 mg·kg⁻¹·d⁻¹) and L-theanine (100 mg·kg⁻¹·d⁻¹) continuously fed by gavage to high-fat diet SPF-grade SD rats for 56 d were compared to investigate the synergistic moderating effects of L-theanine and EGCG for the prevention of obesity and hypercholesterolemia. The results showed that compared with the normal group, there were significant differences (P<0.05) in body weight and blood lipid level in the high-fat diet group, and the body weight had exceeded 21.2% of the weight of the normal group, and the total serum cholesterol exceeded 79.9% of the normal group, indicating that the obesity and hypercholesterolemia model rats were successfully modeled. Compared with the model group, all intervention groups could effectively inhibit the increase of body weight and blood lipid level in rats on long-term high-fat diet; compared with the L-theanine group, the combined EGCG+L-theanine intervention group significantly improved body weight, blood lipid, liver lipid and liver redox status (P<0.05). The combined EGCG+L-theanine intervention group showed better effects on body weight, abdominal fat mass, liver coefficient, organ index, hepatic malondialdehyde content, hepatic peroxidase activity, serum Apo B100 content, Apo B100/A1 ratio, and hepatic lipid accumulation compared to the EGCG group. Compared with the simvastatin group, only the combined EGCG+L-theanine intervention group showed a significant reduction in body weight, abdominal fat mass, and liver TG content (P<0.05); meanwhile, the pathological sections showed a large accumulation of lipids in tissues and organs of rats with long-term high-fat diet-induced obesity and hypercholesterolemia, which was significantly improved in the combined EGCG+L-theanine intervention group. This suggests that L-theanine and EGCG have synergistic regulatory effects in the prevention of obesity and hypercholesterolemia.