Hyperglycaemia in diabetes can cause nitrosative/oxidative stress and subsequent Poly(ADP)Ribose Polymerase (PARP) activation that are implicated in the pathogenesis of microvascular complications. Obstructive sleep apnea (OSA) causes nitrosative/oxidative stress and is common amongst patients with diabetes. We hypothesised that diabetes and OSA together cause greater nitrosative/oxidative stress than either alone and tested this in an acute rat model of hyperglycaemia and airway occlusion. In 26 male Wistar rats anaesthesia was induced with 3.5% isoflurane in oxygen and was maintained by continuous infusion of Alfaxan (5mg.ml-1 at 0.8ml.hr-1 I.V.). Animals were exposed to one of the following four conditions for six hours: normoglycaemia airway unoccluded (NGAU, n=7), normoglycaemia airway occluded (NGAO, n=6), hyperglycaemia airway unoccluded (HGAU, n=7) and hyperglycaemia airway occluded (HGAO, n=6). In all groups blood glucose was monitored throughout the protocol and in HG groups, glucose was administered via the femoral vein to maintain glucose levels at 12mmol.L-1. In AO groups, airway occlusions occurred for 15 seconds every minute by mechanical occlusion of a cannula placed in the trachea. Rats were killed by exsanguination followed by cervical dislocation for confirmation and organs were harvested. 3-nitrotyrosine (NT) levels were measured in plasma samples using commercially available ELISA kits (Oxiselect, San Diego) and liver sections were stained for Poly(ADP)Ribose (PAR) using immunohistochemistry. Values are expressed as means ± S.E.M. and significance (P<0.05) was determined by one-way ANOVA. In control NGAU plasma NT was 88±17 nM; 6 hours of hyperglycaemia or airway occlusion alone did not cause a significant increase in plasma NT (114±19 nM and 149±16 nM respectively), however 6 hours combined hyperglycaemia and airway occlusion did significantly increase plasma NT (289±44 nM, p=0.017). The same response was seen for PAR staining in the liver with combined HG and AO significantly (p<0.001) increasing % PAR stained nuclei (NGAU 19±3 %, HGAU 29±5 %, NGAO 35±3 % and HGAO 49±5 %). In our model, just 6 hours of combined HG and AO increased levels of NT and downstream effects that influence the progression of microvascular complications than either insult alone. This suggests that OSA in patients with diabetes may exacerbate the development of microvascular complications.