To investigate the role of the Toll‐like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2‐, TLR4‐ and MyD88‐deficient mice with the avirulent cyst‐forming Fukaya strain of T. gondii. All TLR2‐ and MyD88‐deficient mice died within 8 days, whereas all TLR4‐deficient and wild‐type mice survived after i.p. infection with a high dose of T. gondii. Peritoneal macrophages from T. gondii‐infected TLR2‐ and MyD88‐deficient mice did not produce any detectable levels of NO. T. gondii loads in the brain tissues of TLR2‐ and MyD88‐deficient mice were higher than in those of TLR4‐deficient and wild‐type mice. Furthermore, high levels of IFN‐γ and IL‐12 were produced in peritoneal exudate cells (PEC) of TLR4‐deficient and wild‐type mice after infection, but low levels of cytokines were produced in PEC of TLR2‐ and MyD88‐deficient mice. On the other hand, high levels of IL‐4 and IL‐10 were produced in PEC of TLR2‐ and MyD88‐deficient mice after infection, but low levels of cytokines were produced in PEC of TLR4‐deficient and wild‐type mice. The most remarkable histological changes with infiltration of inflammatory cells were observed in lungs of TLR2‐deficient mice infected with T. gondii, where severe interstitial pneumonia occurred and abundant T. gondii were found.