The major findings of this study were: (1) the rats with DKD had increased circulating TMAO levels; (2) the circulating TMAO levels of the CON + TMAO rats administered TMAO for 12 weeks were almost the same as those of the DKD rats; (3) TMAO administration in the DKD group decreased the body weights and increased the fasting blood glucose levels of the rats, while it had no effect on TG and TC levels; and (4) TMAO facilitated tubulointerstitial injury and renal fibrosis, and it activated the NLRP3 inflammasome to exacerbate renal inflammation. This evidence concerns the gene NLRP3 and inflammatory response.