This work studied in vitro and in vivo the antibacterial activity of lactoferrin and/or bacitracin against Clostridium perfringens type A in rabbits. C. perfringens was bacteriologically isolated with a total rate of 37% from rectal swabs and fecal matter of diseased rabbits besides intestine of freshly dead. After targeting alpha, beta, epsilon and iota toxins genes by molecular typing (multiplex PCR), all isolates produced only alpha toxin and typed as type A. A total of 35 rabbits were divided into 5 groups; G1: negative control, G2: infected control with C. perfringens type A (1×109 CFU/ml) orally, G3: infected (Bacitracin Methyline Disalicylat BMD) 10 mg/kg body weight), G4: infected (lactoferrin 50 mg/kg body weight) and G5: infected (BMD 5 mg/kg + lactoferrin 50 mg/kg). MIC and MBC were 7.812 and 125 μg/ml for bacitracin, 0.195 and 3.125 mg/ml for lactoferrin respectively. C. perfringens count significantly decreased by all treatments while no bacteria were re-isolated from the liver in G5. All drugs recovered most of the detected parameters especially G4 and G5 reflected a significant increase in TP, albumin, globulin, lysozyme activity, and calcium, while reduced ALT, AST, ALP, LDH, BUN, and creatinine levels than G2. Finally, lactoferrin revealed significant antibacterial activity against C. perfringens either alone or synergistically adjunct with BMD.