MicroRNAs play an important role in the regulation of immune responses. The influence of epigenetic mechanisms, particularly RNA-mediated post-transcriptional regulation of host immune responses has been proven vital following infections by different pathogens, and bacteria can modulated host miRNAs. Global miRNA expression analysis from macrophages infected in vitro with different strains of Leptospira spp was performed using miRNA 4.1 microarray strips. Leptospirosis is a bacterial zoonosis of global importance, responsible for significant morbidity and mortality worldwide. Despite considerable advances, much is yet to be discovered about disease pathogenicity, particularly in regards to host-pathogen interactions. We present here a high-quality dataset examining the microtranscriptome of murine macrophages J774A.1 following 8h of infection with virulent, attenuated and saprophyte strains of Leptospira. Metadata files were submitted to the Gene Expression Omnibus (GEO) repository.