Aim To observe the effects of Xuezhikang on Ca²⁺ concentration and mitochondrial membrane potential in hepatocytes of apolipoprotein E gene-knock out mice. Methods The hepatocytes of ApoE~(-/-) mice were separated with collagenase and cultured in RPMI1640 with 10% fetal bovine serum for 8 days.Then the hepatocyes were incubated in culture medium with 10% Xuezhikang-containing rat serum for 48 hours.Finally,after stained with flou-3/AM and JC-1,the Ca²⁺ concentration and the mitochondrial membrane potential in hepatocytes were detected with laser scanning confocal microscope. Results Xuezhikang could decrease Ca²⁺ concentration in hepatocytes and there was significant difference between Xuezhikang group and control group(p<0.01).Xuezhikang could also improve mitochondrial membrane potential in hepatocytes(p<0.05). Conclusion Xuezhikang can decrease the Ca²⁺ concentration and improve mitochondrial membrane potential in hepatocytes.This may be important mechanisms of Xuezhikang in anti-hyperlipemia.