Lake water is a micro-polluted water system, and characterization of its toxicity remains difficult. Microarray-based determination of altered gene expression might be an alterative approach. We chose raw water from Meiliang Bay, Lake Taihu, China as the target water. Male mice were exposed to the lake water for 90 days. Total hepatic RNA was applied to interrogate the Affymetrix Mouse Genome 430A 2.0 array. Gene ontology analysis, pathway analysis and gene network analysis were used to identify biological effects of differently expressed genes. The results showed that the expressions of 170 genes were altered. Nine biological processes and nine biological pathways were significantly perturbed (P ≤ 0.01), mainly linked to the regulation of cell processes, DNA repair, chromatin modification, oxidative reduction and carbohydrate metabolism. Important genes, such as Prkca, Pik3r1, Fgfr1 and Zbtb16, were identified by gene network analysis. This study provided excellent insights into early toxicological effects related to raw Lake Taihu water, and illustrated that the toxicogenomic approach might be a useful tool to evaluate potential environmental health effects of raw lake water. Copyright © 2012 John Wiley & Sons, Ltd.