Typhoid fever is a major cause of morbidity and mortality in the developing world. Data from World Health Organization (WHO) shows that 21 million cases of typhoid occur globally every year and over 200,000 die each year; most of them at a very young age. The situation in Pakistan is similar. Typhi and other typhoidal salmonellae have developed resistance to chloramphenicol and other first line anti-typhoid. There is a rapid increase in multi-drug resistance (MDR) throughout the world. There is an urgent need to find out alternative medicine to sort out this problem. This study was conducted to establish preventive as well as therapeutic potential of Manuka honey. A total of eighty pathogen free BALB/C mice between 8 weeks to 12 weeks of age, weighing 25-30 grams were taken and divided into 4 groups. Group A, B and C were infected through oral route with 10(8) colony forming unit (CFU) of Salmonella typhimurium ATCC 14028 to produce typhoid like disease in mice. Group A, which comprised of 20 mice was further divided in A1 and A2 given Manuka honey at a dose of 15ml/kg and 20 ml/kg respectively. Group B, which comprised of 20 mice was further divided in B1 and B2 was given Manuka honey at dose of 20ml/kg and 25ml/kg respectively. Clinical features of mouse typhoid, like body temperature, respiratory rate, number of stools and general behavior were recorded twice daily. Blood cultures of mice in different groups were taken at different days to evaluate the establishment of infection as well as to observe the therapeutic and preventive potential of Manuka honey in mouse typhoid. Fisher's Exact, Chi- Square and t-test were used to analyze the data. Significant association was observed in the ultimate fate of mice in Group A1 and Group A2 (P<0.001), showing that from a total of 20 mice in both groups, 10 mice fall in Group A1 of which 10 (100%) developed infection as it was not prevented by honey at a dose of 15ml/kg body weight (15.00±0.00) in Group A1 and ten mice fall in Group A2 of which 10(100%) did not developed an infection as it was prevented by honey at a dose of 20ml/kg body weight (20.00±0.00) in Group A2. Significant association was observed in the ultimate fate of mice in Group B1 and Group B2 (P<0.001) showing that from a total of 20 mice in both groups, 10 mice fall in Group B1 of which 10 (100%) had an infection, which was not treated by honey at a dose of 20 ml/kg body weight. Ten mice fall in Group B2 of which 10 (100%) had an infection, which was treated by honey at a dose of 25 ml/kg body weight (25.00±0.00). Results of the present study suggest that Manuka honey (UMF25±) has a potent anti-typhoid activity in vivo as well. There is an intense need for a carefully designed clinical trial in which this therapeutic potential of Manuka honey should be further evaluated. There is also need for the search of local honeys comparable to Manuka honey as a therapeutic option for typhoid fever.