PURPOSE: Renal tubules injury, inflammation can promote crystal nucleation, aggregation and retention.The effect of melamine and cyanuric acid ou renal tubule is unclear, we tested the hypothesis that melamine and cyanuric acid may lead to renal tubular epithelial cell injury, apoptosis and inflammation.MATERIALS AND METHODS: Four-week-old male Sprague-Dawley rats were separated into two experimental groups.Treatment group was administered daily with a standard commercial diet mixing with melamine and cyanuric acid, and control group was given a normal diet.Rat kidney specimens were stained with hematoxylin/eosin, and crystals were examined using a polarizing microscope.Transmission electron microscopy was pertormed on kidney tissue obtained from rats treated with melamine and cyanuric acid for 4 weeks.Total RNA was extracted from tissues, Semiquantitative RT-PCR assay was performed to determine MCP-1 mRNA expression.Apoptotic cells were examined by TUNEL assay.RESULTS: All five rats in treatment group were detected microscopic hematuria after administering for four weeks.The body weight of treatment group rats (142.1±26.7g) was significantly lower than of control group (196.4±31.8g,p=0.02).The kidneys of the treated groups were found to be edematous, and the surface of kidney were observed widely brownish-yellow precipitate.Melamine-associated crystals formed in wide renal tubue segment including glomerulus, proximal convoluted renal tubule, distal convoluted renal tubules, the limb loops of Henle and medullary collecting ducts in the cortex and medulla area.Crystals lead to tubular lumen dilatation and tubular epithelial cell necrosis.Cell nucleus in the renal tubular cell were found to be condensed or peripheralized chromatin under the nuclear membrane.Cell nucleus outlines became irregular, lysosomal-related structures increased.Renal tubules epithelial cells were observed disappeared structure, numerous cytoplasmic vacuoles and shortening and loss of basal infoldings.Apoptotic body containing organelles or nuclear materia could be found in tubular lumen.MCP-1 mRNA expression was increased.CONCLUSIONS: Melamine and cyanuric acid may lead to renal tubular epithelial cell injury, apoptosis and inflammation.