[Abstract ] Objective Liver cirrhosis modeling with carbon tetrachloride (CCL4) may be influenced by many factors, such as drug concentration and dosing methods.In this article, we explored the influences of different concentrations and different dosing methods and time of CCL4 on the induction of liver cirrhosis in rats. Methods We constructed rat models of liver cirrhosis with different con-centrations of CCL4(30%and 50%), using different dosing methods (subcutaneous injection, intraperitoneal injection, and intragastric administration) , and for different lengths of dosing time (8 wk, 10 wk, and 12 wk) .We collected blood and liver tissues from the rats at different time points for HE and MTC staining, biochemical and histomorphological scores based on the Scoring Model for Liver Cirrho-sis Disease (SLCD, expressed by R) and the Laennec Fibrosis Scoring System (LFSS, expressed by L), and analysis of the results by 3 ×2 ×3 factorial experiment design. Results The R value was lower in the intraperitoneal injection than in the subcutaneous injection and intragastric administration groups, and so was it in the 50% than in the 30%CCL4 group, decreasing with the extending of dosing time, with statistically significant differences in the main effects ( P<0.05) as well as a remarkable correlation among drug concentrations, dosing methods, and dosing time (P<0.05).The L value was higher in the intraperitoneal injection than in the subcutaneous injection and intra-gastric administration groups, and so was it in the 50% than in the 30% CCL4 group and in the 12 wk than in the 10 wk and 8 wk groups, with statistically significant differences in the main effects ( P<0.05) but no remarkable correlation among drug concentrations, dosing methods, and dosing time ( P>0.05) .The death rate showed an increasing trend in the intraperitoneal injection, subcutaneous injection and intragastric administration of 30% CCL4 (25.33%, 37.78%, and 38.37%) and 50% CCL4 (42.97%, 47.85%, and 51.88%), higher in the 50%than in the 30%CCL4 .However, no significant differences were found in the survival curves among differ-ent dosing methods or between different drug concentrations (P>0.05). Conclusion Intraperitoneal injection was better than subcu-taneous injection and intragastric administration of CCL4 in inducing liver cirrhosis, and the three dosing methods all showed progressively improved efficiency of modeling with the increase of drug concentration and dosing time.