Abstract Background. We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. Methods. Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg −1, i.p.) 5 weeks prior to the experimental session. Diabetic animals had blood glucose levels (BGLs) higher than 350 mg dl −1. Randomly chosen rats were treated with insulin (4 IU day −1rat −1) starting 1 week after STZ. Animals were given 1 ml of 0.6 m HCl by gavage following 18 h of fasting. Normal feeding was started 1 h later. Animals were killed at various time points after HCl. Recombinant human IGF-1 (rhIGF-1) at doses 10–400 μg kg −1was injected subcutaneously twice daily for 4 days following HCl treatment. Results. Gastric lesions induced by HCl healed macroscopically within 10 days. DM and insulin regimen did not affect the development of HCl-invoked gastric lesions. However, DM significantly delayed the healing of such lesions. Daily administration of insulin returned the high BGLs to significantly lower ranges (190–210 mg dl −1) and markedly antagonized the delayed healing. Likewise, the repeated administration of rhIGF-1 (≥10 μg kg −1) significantly enhanced the healing of gastric lesions in diabetic rats, without any notable effect on BGLs or gastric acid secretion. The mucosal expression of IGF-1 mRNA was lower in diabetic rat stomachs as compared to normal rats, although the expression was apparently restored after insulin treatment. Conclusion. These results suggest that DM has a deleterious influence on the healing of acute gastric lesions in both insulin- and IGF-1-sensitive manner. The systemic administration of rhIGF enhanced the rate of healing of gastric lesions observed in the healing-impaired STZ-diabetic animals.