Studies on the incidence of diabetes and asthma together, indicate that they seldom occur in the same patient. If asthma develops in diabetic patients it is less severe than that in the residual population (1). Our aim was to investigate whether diabetes, modulates/alters the bronchial responses in hypereactive airway smooth muscle (ASM) and whether the two of the epithelium mediated pathways: COX, and EpDHF were affected. Experimental models of guinea pigs (n=30) with airway hyperreactivity (ovalalbumin (20mg/kg), ip for two alternate days), and diabetic guinea pigs along with airway hyperreactivity (streptozotocin (180mg/kg (2)), four weeks after ovalbumin, ip for two alternate days) were developed. Numerical data is expressed as mean ± SEM of the number of animals used in each experiment. The results were analyzed by one way analysis of variance (ANOVA) followed by post-hoc Tukey’s test. Differences were considered statistically significant at p<0.05. Denudation of tracheal rings from healthy guinea pigs significantly reduced the IP induced relaxation response, suggesting that the relaxant response to IP is mediated in part through the epithelium. When the same experiment was repeated on the epithelium intact trachea of guinea pigs with hypereactivity, a smaller response to IP was produced, indicating partial loss of epithelium mediated relaxation. A significantly smaller relaxation response was observed in guinea pigs with diabetes along with airway hyperreactive condition to IP in comparison to healthy and hypereactive guinea pigs (Fig 1) suggesting that diabetes worsens the loss of epithelium mediated relaxation. Epithelium denudation did not alter the IP induced relaxant response in guinea pig with diabetes and airway hyperreactivity validating complete loss of epithelium mediated relaxation (Fig 2). The relaxant response to IP in presence of glibenclamide was significantly reduced in healthy trachea (14.7±1.2%, *p<0.05), but not in the hyperreactive trachea (4.6±0.6%) and in diabetes along with airway hyperreactive trachea (3.5±0.9%). The results suggest that in both hypereactivity and diabetes along with hyperactivity EpDHF pathway was damaged. The relaxation response of healthy trachea (14.5±1.2%, *p<0.05) and hyperreactive trachea (9.6±2.2%, p<0.05) to IP after addition of indomethacin, significantly reduced. In contrast, there was no alteration in the relaxant response to IP in trachea where diabetes occured along with with airway hyperreactivity (3.2 ±1.4%), after incubation with indomethacin. This implies that diabetes aggravates epithelial dysfunction by disrupting the COX pathway in diabetes along with hyperactivity. Therefore we can conclude that diabetes further deteriorates the epithelium mediated bronchiorelaxation, specifically the COX mediated pathway in the guinea pigs having both diabetes and airway hyperreactive condition.