Background: Pre-clinical and clinical studies have shown that inflammatory pain intensity is increased under diabetes condition. Open cholecystectomy (OC) is a surgical procedure with predictable postoperative pain. However, the comparison of postoperative pain due to open cholecystectomy in diabetic and non-diabetic patients remains unknown. The research question to answer was whether diabetic patients undergoing OC development greater intensity of postoperative pain than non-diabetic patients. Methods: The study was conducted between June 2016 and February 2018 at the Regional Hospital of High Specialty "Dr. Juan Graham Casasús" of Villahermosa, Tabasco, Mexico. Seventy patients in two groups of 35 patients each scheduled for OC under general anesthesia were studied. Pain was assessed using the 11-point numerical rating scale (NRS). The primary endpoint was to know NRS pain scores after awaking of general anesthesia. Secondary outcomes included the time of onset of pain and comparing NRS scores between diabetic and non-diabetic patients undergoing OC. Results: Diabetic patients reported significantly greater intensity pain than non-diabetic patients. The mean overall pain score in the diabetic and non-diabetic patients was 7.2 ± 0.3 and 5.3 ± 0.3 (P = 0.0002), respectively. Furthermore, 60% of diabetic patients had severe pain (NRS ≥ 8) compared to 20% of non-diabetics (P = 0.006). The time to onset postoperative pain was about 35 minutes in both groups (P = 0.876). Conclusions: Diabetic patients undergoing OC have greater intensity postoperative pain and also more frequency of patients with severe pain