Hypertension (HTN) and diabetes (DM) are comorbid conditions, each associated with inflammation. Lipopolysaccharide (LPS) is elevated in the serum of patients with DM and capable of robustly activating the immune system. Risk of erectile dysfunction (ED) is increased in both HTN and DM. Vascular relaxation is needed to regulate vascular tone and erectile function. Our previous studies showed that corpus cavernosum (CC) nitrergic relaxation to electrical field stimulation (EFS) was reduced after LPS exposure. It is not known whether LPS-induced inflammation plays a role in DM-associated ED. Our study aim was to examine vascular function of rat CC under high glucose conditions in the presence of LPS. We hypothesized that high glucose would exacerbate the LPS-induced decrease in EFS relaxation. Isolated rat CC strips incubated with control (5mM) or high glucose (HG, 25 mM) media with or without LPS (1 ug/mL) for 6 h. CC strips were mounted in a myograph and pre-contracted with phenylephrine (PE, 10-5 M) before eliciting relaxation responses using 20-volt stimuli of 1, 2, 4, 8, and 16 Hz. Four Hz produced the half maximal response (%PE contraction) and was used to compare treatment effects. LPS-treated CC (7.13±1.53%) relaxed less than Control CC (19.1±2.67%). The decrease in relaxation was greatest in HG+LPS-treated CC (-3.58±1.43%), Fig. 1. Thus, we show that the LPS-induced reduction in relaxation is exacerbated in the HG+LPS condition, suggesting that elevated LPS and hyperglycemia act synergistically in the promotion of vascular dysfunction and ED.