Salmonella, major food-borne illness among human and animals where poultry being primary source of infection. Current strategies, vaccination, antibiotics, feed additives, help to reduce the infection in poultry but insufficient for long-term protection. This study's aim to compare the efficacy of three antibiotics used for salmonellosis treatment in poultry. Experimentally, rabbits (n=12) 8 weeks old, were divided into four (4) groups (A, B, C and D), three animals in each group. Animals initially kept for five days in their respective wooden cages, fed on commercial diet. The blood samples from typhoid infected human patients (n=5) were collected from Jinnah hospital Lahore to isolate bacteria by culturing on blood agar media. Culture filtrate (5 mL) of salmonella typhi was injected to experimental rabbits except control group. After 48 hours collected blood samples of three antibiotics treated groups were subjected for genomic DNA isolation, PCR amplification of flipC gene. For experiment trail, the experimental groups were subjected on three antibiotics treatments with oral dose (50mg/kg) for ten days. Group-A (control) untreated, group-B (ciprofloxacin), group-C (azithromycin) and group-D (cefotaxime). During drug delivery, feces of rabbits were collected on 1st, 4th, and 7th day for comparative analysis of drug efficacy by calculating CFU/mL grown on blood agar medium. Body weight analysis showed an increase in weight of untreated group while gradual decrease for experimental groups, which indicated the effect of infection and poor absorption of nutrients. Salmonella infection was confirmed through PCR gene mapping test which was observed in all infected animals. Lesser CFU/mL (68.33) with grey-white colonies were observed in animal of group-B, 107 CFU/mL with opaque colored colonies (group-C) and 89 CFU/mL with moist, circular, smooth convex surface colonies (group-D). Thus ciprofloxacin (group-B) revealed as most effective antibiotic against Salmonella infection with more efficacy. These findings would be helpful for the farmers to use this antibiotic at poultry flocks against salmonellosis.