To describe gene expression changes that characterize the development of diabetic nephropathy, we performed microarray analysis on kidney glomeruli by laser capture microdissection from OVE 26 diabetic and control FVB mice. Preliminary data suggest that two rounds of transcript amplification can generate accurate and reproducible gene expression profiles, starting with as little as 20 ng of total RNA. Total RNA extracted from CapSure LCM caps was consistently high quality with strong 18S and 28S bands in every sample as analyzed by the Agilent 2100 bioanalyzer system. A triplicate of one mouse was analyzed in each group. To analyze overall changes in diabetic mice, microarray data were analyzed in MAS 5.0 and all samples were scaled to a signal mean value of 150 and imported into Partek Pro 6.0. T-test enabled the identification of genes that were differentially expressed. Using selection criterion p<0.005, 132 genes were identified. A total of 35 genes had higher expression by more than 1.5 fold in the diabetic OVE 26 mice compared with nondiabetic control mice (p<0.005). In contrast, 70 genes had lower expression by more than 1.5 fold in diabetic OVE 26 mice compared with controls (p<0.005). These genes are from diverse functional groups including oxidative phosphorylation, transcription and translation, protein trafficking, channels, pumps and immune function.