Introduction Diabetic complications as peripheral neuropathy and delayed wound healing affect patient’s quality of life and may lead to amputation. Several mechanisms are involved in mediating these complications including accumulation of Advanced Glycation End Products (AGEs) and the subsequent state of inflammation which were investigated in the current study. Methos A wound of fixed size was induced in STZ-diabetic rats and the effect of diabetes and treatment with glimepiride, α-lipoic acid and pyridoxamine on the levels of glucose, insulin, HbA1c, AGEs, RAGE, sRAGE, TNF-α and adiponectin were investigated. Also the latency time in the hotplate test and wound healing were quantified at different time points. Results Our results have shown that STZ induced a condition of diabetes (elevated glucose, HbA1c, and reduced insulin), enhanced AGEs signaling (elevated AGEs, RAGE, and reduced sRAGE) and inflammation (elevated TNF-α and reduced adiponectin), accompanied by hyperalgesia and delayed wound healing, while all treatments were able to ameliorate most of these effects. Conclusion These results confirm the involvement of AGEs signaling in mediating diabetic complications and suggest their possible use in the standard therapy for diabetic patients.