Background: Contrast-induced nephropathy (CIN) remains a significant complication in patients undergoing percutaneous coronary intervention (PCI), particularly among those with diabetes mellitus (DM). Colchicine, a potent anti-inflammatory agent, has been hypothesized to reduce the incidence of CIN through its anti-inflammatory properties. Objective: This study aimed to evaluate the effectiveness of colchicine loading in reducing the incidence of CIN in diabetic patients undergoing elective PCI. Patients and methods: A simple random sampling method was used, employing a computer-generated table. A total of 200 diabetic patients complaining of chronic coronary syndrome and scheduled for elective PCI were randomly assigned to receive an antihistamine, an antiemetic, and a colchicine loading dose of 1.5 mg administered 1 to 2 hours before PCI, with an additional 0.5 mg of colchicine given either 1 hour after or immediately following the procedure or to standard clinical practice, which included antihistamine and antiemetic without colchicine. The patients were randomized into two groups: the colchicine group (n=100) and the control group (n=100).  Results: The primary endpoint, CIN incidence, was significantly lower in the colchicine group (12%) compared to the control group (28%) (P=0.005). Serum creatinine 48 hours post-contrast was significantly lower in the colchicine group (0.88 ± 0.22 mg/dL) compared to the control group (1.01 ± 0.24 mg/dL, P=0.006). Similarly, eGFR was notably higher in the colchicine group (77.76 ± 14.70 ml/min) than in the control group (70.20 ± 17.38 ml/min, P=0.021). Conclusion: Colchicine loading before PCI significantly reduced the incidence of CIN in diabetic patients, suggesting a potential role for colchicine in protecting renal function in this high-risk population.