The diet and breeding patterns of Mastomys natalensis in semi-arid areas of Isimani division, Iringa region, Tanzania were investigated in maize fields and fallow land. The aim was to investigate the influence of diet on breeding patterns of M. natalensis. Removal trapping was used to capture rodents and analyse diet categories while Capture-mark-release trapping was used to investigate breeding patterns of female M. natalensis. Mastomys natalensis comprised 94% of the total capture, and the remaining 6% comprised of six other species. Statistical analysis of food preferences indicated that both vegetative materials and seeds were significantly higher in the overall diet of M. natalensis compared with other food materials. Significant differences in the proportions of vegetative materials and seeds were found between seasons (dry, wet), but not between habitats (fallow, maize). There was a clear seasonal pattern in the proportion of reproductively active females with peaks in April and troughs in October. The proportion of vegetative materials was highest during the wet season and correlated positively with reproductive activity, suggesting that vegetative materials contain certain compounds (e.g. 6-MBOA) that trigger reproductive activity in M. natalensis. The breeding activity of M. natalensis in semi-arid areas might, thus, be reduced by limiting access to fresh vegetative food (e.g. young sprouting grass).