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Background: Hyperlipidemia is an important risk factor for cardiovascular diseases. In this study, the effects of physalis alkekengi extract on the levels of cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (TG) were evaluated. Materials and Methods: In this experimental study, fifty adult male Wistar strain rats were selected and divided into five groups of ten: Control group with a normal diet, control group with a high fat diet receiving interpritoneal injection of saline for 21 days, and treatment groups with fatty diets which received maximum (0.1 g/kg), moderate (0.2 g/kg), and minimum (0.4 g/kg) dose interpritoneal injections of the extract. After this period, blood sampling was done and the obtained results were analyzed through SPSS software. Results: According to the obtained results, LDL and cholesterol concentrations decreased significantly (P<0.05), whereas HDL and TG plasma concentrations did not reveal any significant changes. Conclusion: The findings of this study show that such changes are mainly due to the lycopene existing in the plant. Lycopene is a strong antioxidant which inhibits the production of LDL and presumably increases the excretories through releasing cholesterol therefore, it reduces blood cholesterol level and controls cholesterol synthesis.