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Genistein is a natural isoflavonoid and has several pharmacological effects, such as antioxidant, antitumor activity, and improvement of glucose metabolism. The safety of intestinal anastomosis after ischemia-reperfusion (I/R) injury is a critical issue for surgeons. This experimental study aimed to investigate the effects of genistein on anastomotic healing after intestinal I/R injury.A total of 36 male Wistar Albino rats were divided into four groups: control, I/R, genistein, and genistein + I/R. The control group received segmental ileal resection and ileoileal anastomosis. The I/R group received resection + anastomosis after intestinal I/R. The genistein group was administered subcutaneous injection of 1 mg/kg genistein 12 h and 1 h before the procedure and received ileal resection + anastomosis. The genistein + I/R group received I/R + ileal resection + anastomosis after genistein injection. Anastomotic bursting pressure, hydroxyproline, superoxide dismutase, and glutathione peroxidase levels and histopathological wound healing scores of all rats were measured on postoperative day 5.The anastomotic bursting pressure was significantly higher in the genistein and genistein + I/R groups (P 0.001). Genistein increased the hydroxyproline concentration and the superoxide dismutase and glutathione peroxidase levels in the intestinal anastomosis (P 0.001). In histopathological assessment, the mean wound healing score was significantly higher in the genistein group than in the other groups (P 0.001).Genistein, with its anti-inflammatory and antioxidant properties, shows protective effects against increased oxidative stress after intestinal I/R injury and contributes positively to intestinal anastomotic healing.