Objective       To explore the role of p38MAPK signaling pathway in rosiglitazone (ROZ)-induced cell cycle arrest in human hepatocellular carcinoma cell line HepG2.       Methods       HepG2 cells were treated with different concentrations of ROZ. The proliferation inhibitory rates were analyzed by MTT assay. Cell cycle distributions were detected by flow cytometry (FCM). Western blotting was used to detect the expression of proteins related to p38MAPK signaling pathway.       Results       ROZ significantly inhibited proliferation of HepG2 ce

lls

and induced an increase in the percentage of G

0

/G

1

phase cells and a decrease in the percentage of S phase cells accompanied by the change in DNA ploidy (

P

0.05). ROZ increased p38MAPK phosphorylation but not ERK1/2 or JNK phosphorylation

and up-regulated the protein expression levels of p-p53 and p21 in HepG2 cells (

P

0.05). In addition

the ROZ-induced cell proliferation inhibition and cell cycle arrest were partly blocked by p38MAPK inhibitor SB203580

as well as the changes of p-p53 and p21 proteins.       Conclusion       ROZ inhibits cell proliferation and induces cell cycle arrest in G

0

/G

1

stage of HepG2 cells by the activation of p38MAPK pathway

which may be mediated by the p38MAPK/p53/p21 signaling axis.