In inflammatory conditions, macrophage dominance affects the degree of inflammation. We assessed the effects of the active vitamin D (calcitriol) on inflammatory processes and macrophage dominance and aimed to determine the potential positive macroscopical and histological effects in the supermicrosurgical arterial anastomosis model of rats. Forty rats were divided into five groups: control surgery (Group 1), surgery with preoperative (Group 2), postoperative (Group 3) and peroperative (Group 4) systemic calcitriol, and surgery with local calcitriol (Group 5). Eighty femoral artery anastomoses were planned in both legs of rats. Systemic calcitriol was administered intraperitoneally to the relevant groups daily. Preoperative vessel diameter measurements were taken before anastomosis. Three weeks postsurgery, postoperative vessel diameter measurements were taken, anastomosis patency was assessed, and vascular segments were collected for histological examination, which included assessment of M1 and M2 macrophage depolarization, leucocyte infiltration, intima–media ratio, and luminal gap scoring. Systemic calcitriol administration (pre-, post-, or perioperative) significantly improved vessel diameter (p < 0.001); there was no significant difference among Groups 2–4. Histological findings revealed that Groups 3 and 4 had lower intima–media ratios (p < 0.05 and p < 0.01), higher M2-M1macrophage ratios (p < 0.01 and p < 0.001), and lower leucocyte infiltration (p < 0.05, p < 0.01, and p < 0.001). Local calcitriol administration had no vasodilatory effects or resulted in positive histological outcomes. Although the administration of calcitriol pre- and postoperatively increased vessel diameter, the latter appeared to have a more favorable impact on the histological analyses.