The result of acute exposure of the pancreatic β-cell to high glucose concentrations and/or saturated non-esterified fatty acids NEFA is a substantial increase in insulin release, while chronic exposure leads to desensitization, a reduction in secretion followed by apoptosis. Acute stimulation by some unsaturated NEFA can promote insulin release but they are less toxic to β-cells following chronic exposure and can even exert protective effects. Therefore changes in the levels of NEFA are likely to be important for the regulation of β-cell function and viability under physiologic conditions. In addition, the switching between endogenous FA synthesis or oxidation in the β-cell, together with alterations in neutral lipid accumulation, may have critical implications for β-cell function and integrity. Long Chain Acyl CoA controls several aspects of β-cell function including activation of specific isozymes of PKC, modulation of ion channels, protein acylation, ceramide formation and/or NO-mediated apoptosis, and transcription factor activity. Both the level of saturation and chain length appear to be critical in determining signaling and functional outcome (1). In the present study, the effects of chronic exposure (24hr) to the polyunsaturated fatty acid, Arachidonic acid (AA) were studied using the clonal BRIN BD11 β-cell line. Gene expression profiling of BRIN BD11 cells exposed for 24 hours to 100 μM AA was conducted using microarray analysis. Culture for 24 hours in 100uM AA compared to control resulted in significant (using the Bioconductor software package) changes in 3 genes. Stearoyl-CoA dehydrogenase and ATP-binding cassette, sub-family G (WHITE) member 1 expression were downregulated 3.87 and 1.7 fold respectively. On the other hand Enoyl Coenzyme A hydratase 1, expression was upregulated 1.73 fold relative to control. Subsequent experiments were carried out to establish if the effects were long chain polyunsaturated fatty acid specific. ROS generation which we have previously demonstrated to be NADPH oxidase dependent in the BRIN BD11 cell line (2), was determined after incubation for 24hour in the presence of 100μM palmitic acid (PA) or 100μM AA. We have determined that β-cell ROS production was regulated by type and degree of saturation of the fatty acids tested.