This study aimed to investigate the changes and functions of TRPC6(transient potential canonical 6)in diabetic wounds and the regulatory role of hucMSC-Ex(human umbilical cord mesenchymal stem cell derived exosome)on TRPC6.Tissue immunofluorescence was used to detect the expression of TRPC6 in clinical patients with DFU(diabetic foot ulcer).qRT-PCR and Western blot were used to detect the changes of TRPC6 mRNA and protein expression in rat DFs(dermal fibroblasts)after stimulation with AGE-BSA(bovine serum albumin modi-fied with advanced glycosylation end products),respectively.Moreover,DFs were transfected with siRNA(small interfering RNA)and overexpressed plasmid to investigate the effects of TRPC6 on the biological functions of DFs,such as Ca2+influx,proliferation,and collagen secretion.Cellular immunofluorescence was used to detect the effect of hucMSC-Ex on the ability of DFs to secrete collagen.A DFU model was constructed in SD rats,and hucMSC-Ex was added to intervene,and the skin structure was observed by HE staining,to evaluate the therapeutic effect of hucMSC-Ex on DFU.Furthermore,qRT-PCR,Western blot,cellular immunofluorescence,and immunohistochemi-cal staining were used to detect the effect of hucMSC-Ex on TRPC6.The results showed that TRPC6 channel pro-tein was significantly decreased in diabetic wounds.Knock-down of TRPC6 decreased Ca2+influx and impaired the biological function of DFs.On the contrary,overexpression of TRPC6 enhanced Ca2+influx and biological function of DFs.In conclusion,hucMSC-Ex could regulate TRPC6-mediated Ca2+influx promote diabetic wound healing.