Intranasal administration of lipid microspheres (LM) containing rifampicin (LM-RFP) exhibited the bacteriostatic effect against Mycobacterium tuberculosis H37Rv. The efficacies of intranasal LM-RFP in lung were markedly higher in immunodeficient BALB/c nude mice (p<0.001), but not different in immunocompetent BALB/c mice (p = 1.000) compared to the results of oral rifampicin groups. When intranasal LM-RFP was given instead of oral rifampicin, the reductions of C(max) and AUC(0-3) of nevirapine were decreased from 32.2% to 11.9% and 30.5% to 12.4%, respectively. These results suggested that intranasal LM-RFP could improve the anti-tuberculosis activity in immunodeficient host and minimize drug interaction between rifampicin and nevirapine.