Background and Aims: Studies have demonstrated that caveolin-1 is associated increased angiogenesis, and also closely related to the pathological process of diabetes. Based on speculation that caveolin-1 may play a role in diabetic lower limb ischemia, this study conducted an experiment in acute lower limb ischemia in diabetic rats to investigate its effect and mechanism. 
Methods: Eighty healthy male SD rats were used to construct diabetes models by STZ induction. Then, rats with successful modeling were randomly divided into 4 groups, and underwent femoral artery isolation only (sham operation group), division of the femoral artery and its branches (model group), division of the femoral artery and its branches plus tail vein injection of plasmid containing caveolin-1 (transfection group), and division of the femoral artery and its branches plus tail vein injection of liposome solution without caveolin-1-bearing plasmid (empty transfection group), respectively. After 14 days, gastrocnemius muscle tissues in rats of each group were harvested, the morphological alterations and infiltration of inflammatory cells were observed by HE staining, the NO level was detected by ELISA assay, and the expressions of caveolin-1 and eNOS as well as the CD34 marked microvascular density (MVD) were determined by immunohistochemical staining, respectively. 
Results: Compared with sham operation group, obvious atrophy and marked inflammatory cell infiltration of the gastrocnemius muscle tissue were observed in model group and empty transfection group, while the muscle atrophy was not obvious and inflammatory cell infiltration was attenuated in transfection group; the NO levels in the gastrocnemius muscle tissue of model group and empty transfection group were significantly decreased, while the NO level in transfection group was significantly increased (all P<0.01); the expression levels of caveolin-1 in model group, empty transfection group and transfection group were all increased, but the increasing amplitude in transfection group was significantly greater (all P<0.01); the expression levels of eNOS showed no significant differences in model group and empty transfection group (both P>0.05), but was significantly increased in transfection group (P<0.01); the MVD values in model group, empty transfection group and transfection group were all increased, but the increasing amplitude in transfection group was significantly greater (all P<0.01). All differences in above parameters showed no statistical significance between model group and empty transfection group (all P>0.05).
Conclusion: The high expression of caveolin-1 can effectively improve the diabetic lower limb ischemia, and its mechanism may be related to its activating eNOS/NO pathway and thereby increasing the NO production.