Abstract: Objective To evaluate the efficacy and safety of combination therapy with atorvastatin plus fenofibrate in rats with combined hyperlipidemia. Methods Sixty Wistar rats were randomized into normal group,control group,atorvastatin group,AFH group and AFF group,and fed with high fatty food,except for normal group. At end of week 4,rats in atorvastatin group were given atorvastatin 1.8mg/（kg·d）, rats in AFH group were administered atorvastatin 0.9mg/（kg·d） + fenofibrate 18mg/（kg·d）, and rats in AFF group received atorvastatin 0.9mg/（kg·d） + fenofibrate 18mg/（kg·d）. Levels of TC,TG,LDLC,HDLC,CK,Mb,K⁺ were measured at the end of weeks 4 and 8,respectively. Results The levels of LDLC,and TG were obviously lower in AFH and AFF groups than in atorvastatin group（P＜0.01）. However,the level of HDLC was higher in AFH and AFF groups than in atorvastatin group（P＜0.01）. The level of CK,Mb,K⁺ was significantly higher in AFH group than in other groups（P＜0.01）. Conclusion Combination therapy with atorvastatin plus fenofibrate can decrease the TG and LDLC level,and increase the HDLC level. The negative effects of combination therapy are related to the doses of fenofibrate and atorvastatin,thus drugs should be administered from low to high doses in order to reduce the CK,Mb and K⁺ level.