The mechanism by which baicalin modulated the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was investigated in a rat model of acute endo-toxemia induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion (measured as the stable degradation production, nitrites). LPS not only increased toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma (PPARγ) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPARγ via phosphorylation. Inhibition of p38 signalling pathway by chemical inhibitor SB202190 and small interfering RNA (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARγ pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I) attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and (II) ameliorated LPS-elicited TLR4 and PPARγ production, and (III) inhibited p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV) prevented PPARγ from phosphorylation contributing to maintainence of PPARγ bioactivity. However, SR-202 co-treatment (I) partially abrogated the inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum via inhibition of p38 signalling cascade and activation of PPARγ pathway. There existed a interplay between the two signalling pathways.