Insulin resistance (IR) is a multifactorial syndrome, characterised as a clustering of factors including obesity and hyperglycaemia.  The hallmarks of IR are also known cardiovascular risk factors.  Endothelial Nitric Oxide (eNO) functions to control vascular resistance and is deemed vasoprotective. eNO is produced by the enzyme eNOS.  Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of eNOS.  It has been hypothesised that one cause ofendothelial dysfunction may be an elevation in plasma levels of ADMA.  Approximately20% of ADMA is cleared by the kidney, whereas the remainder is metabolized by theenzyme dimethylarginine dimethylaminohydrolase (DDAH).  We hypothesized that abnormalities in the tissue enzyme DDAH are associated with insulin resistance and cardiovascular risk factors.  We aimed to examine the effect of various factors involved in insulin resistance on DDAH expression and activity using an in-vitro human hepatocyte cell culture model.  HepG2 cells were exposed to either elevated glucose (25mM, 0-12 hours), Insulin (1uM, 0-12 hours), ADMA (3uM and 100uM, 12 hours) and oxidant stress (H₂0₂). Protein was extracted and DDAH expression levels determined by Western immunoblotting. DDAH activity was determined using a colourimetric activity assay.  In this study it was found that DDAH protein expression was significantly increased in response to elevated glucose and there was a significant change in DDAH protein activity (P < 0.05).  DDAH activity was also increased in response to supraphysiological concentrations of ADMA (100uM, P < 0.05) with no change in protein expression.  There was no significant change in DDAH protein expression or activity following either treatment with insulin or oxidant stress.   This study demonstrated the increase in DDAH expression and activity in response to elevated glucose and DDAH activity in response to elevated ADMA.  These results indicate a possible role for DDAH in the control of endothelial function in insulin resistance.