The hepatoprotective effects of Methanolic Extract of Justicia Beddomei (MEJB)on Isoniazid and Rifampicin (INH and RIF) induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. Male wistar rats were divided in to five groups and used for the study. Hepatotoxicity was induced in animal models and was compared with the protective effect of standard drug Silymarin. In the present study it was noted that the administration of INH, Rifampicin decreased the level of total protein, albumin and increased the level of liver enzymes AST, ALT, ALP and TC. These parameters were brought back to the near normal level in control group treated with MEJB. The histopathological studies also revealed that treatment with Methanolic Extract of Justicia Beddomei (MEJB) showed a protection against injuries due to the effect of INH, Rifampicin. These results suggets that MEJB showed significant hepatoprotective activity against Isoniazid and Rifampicin induced hepatotoxicity and this might be due to the presence of flavanoids and phenolics. Further research is sought to explore the mechanism of action and phytoconstituents responsible for the pharmacological action.