We studied roles of phospholipase A2 (PLA2) isozymes, including type IIA secretory PLA2 (sPLA2-IIA), type IV cytosolic, Ca2+-dependent PLA2 (cPLA2) , type V secretory PLA2 (sPLA2-V) , and type VI cytosolic, Ca2+-independent PLA2 (iPLA2) , in macrophage (Mφ) antimicrobial activity against Mycobacterium tuberculosis (Mtb) H37Ra (avirulent) strain and Mφ mRNA expression of these PLA2 isotypes in response to infection with the microorganisms. First, a cPLA2 inhibitor arachidonyl trifluoromethylketone mildly reduced Mφ anti-Mtb activity, while the other PLA2 inhibitors did not significantly block the Mφ antimycobacterial function, if any. Second, Mφ expression of cPLA2 and sPLA2-V mRNAs was up-regulated during 6 to 12 h after infection with Mtb H37Ra strain. These findings suggest that cPLA2 plays a role in cellular mechanisms participating in the expression of Mφ anti-Mtb activity.