Introduction and objectives: The purpose of the study was to observe different expression of connexin 43 between culprit arteries and nonculprit arteries in ischemia-reperfusion model and investigate on the mechanism of nonculprit arteries lesions progression. Methods: Rabbit hyperlipidemia ischemia-reperfusion model was established, vascular smooth muscles of culprit arteries and nonculprit arteries were divided into 4 groups: (1) culprit arteries control group, (2) nonculprit arteries control group, (3) culprit arteries ischemia-reperfusion group, (4) non-culprit arteries ischemia-reperfusion group. Immunohistochemistry analysis of connexin 43 was performed in each group. Smooth muscle cells of nonculprit arteries were divided into 4 groups: (1) normal control group. (2) hyperlipidemia control group. (3) angiotensin II intervention group. (4) mitogen-activated protein kinase pathway inhibitor pretreatment plus angiotensin II intervention group. Expression of connexin 43 was analysed in each group. Results: Fluorescence immunohistochemistry analysis of connexin 43 showed there was significant difference between culprit arteries ischemia-reperfusion group and nonculprit arteries ischemia-reperfusion group (1723.52 +/- 138.64 vs 2136.15 +/- 237.82, P<0.001). Expression of connexin 43 in angiotensin II intervention group was higher than that in hyperlipidemia control group (1.79 +/- 0.31 vs 1.25 +/- 0.21, P<0.05), expression of connexin 43 in mitogen-activated protein kinase pathway inhibitor pretreatment plus angiotensin II intervention group was lower than that in angiotensin II intervention group [(0.85 +/- 0.19 vs 1.79 +/- 0.31, P<0.05), (0.99 +/- 0.13 vs 1.79 +/- 0.31, P<0.05), (0.81 +/- 0.15 vs 1.79 +/- 0.31, P<0.05) respectively]. Conclusions: Expression of connexin 43 in nonculprit arteries was higher than that in culprit arteries, it may be involved in angiotensin II--mitogen-activated protein kinase pathway.