This　study　was　conducted　to　investigate　the　effect　of　tetramethylpyrazine　(TMP)　on　CCl4-induced　fibrosis　in　rats　and　the　possible　roles　of　leptin,　TGF-beta　1,　Smad3,　and　Smad7　in　this　process.　Liver　fibrosis　in　rats　was　induced　by　the　subcutaneous　injection　of　60%　CCl4　(0.3　mL　/100g　body　weight,　biweekly)　for　12　weeks.　Rats　in　TMP　prevention　and　treatment　groups　were　given　TMP　(10　mg　/100　g　body　weight,　daily)　by　gavage　from　days　1　and　31　after　the　start　of　CCl4　injection,　respectively.　The　mRNA　expression　of　leptin,　OB-Rb,　TGF-beta　1,　and　TGF-beta　RII　in　the　liver　were　detected　by　RT-PCR,　whereas　Smad3　and　Smad7　protein　were　determined　by　Western　blot.　The　results　showed　that　hepatic　cirrhosis　was　obviously　alleviated　in　both　TMP　prevention　and　treatment　groups.　The　mRNA　expression　of　leptin,　OB-Rb,　TGF-beta　1　and　-beta　RII,　and　Smad3　protein　were　higher　in　the　cirrhotic　models.　In　TMP　prevention　and　treatment　groups,　these　markers　of　expression　were　higher,　compared　with　that　of　the　normal　control,　but　were　lower　when　compared　with　that　of　the　cirrhotic　model　group.　Smad7　protein　expression　was　lower　in　the　cirrhotic　model　group　than　in　the　normal　control.　Smad7　expression　in　TMP　prevention　and　treatment　groups　was　higher,　compared　with　that　in　the　cirrhotic　model　group.　Liver　collagen　in　the　TMP　prevention　group　was　the　lowest　among　all　CCl4　injection　groups.　In　conclusion,　TMP　can　prevent　and　alleviate　the　development　of　liver　fibrosis　in　rats.　The　possible　mechanism　could　involve　the　downregulation　of　leptin,　Ob-Rb,　TGF-beta　1,　TGF-beta　RII,　and　Samd3,　and　upregulation　of　Smad7.