Preterm babies are susceptible to respiratory infection due to immature lung and immune system. Immune cells express Toll-like receptors (TLRs), which may be important in local host defense of preterm infants. We studied the expression of TLR2 and TLR4 in lung tissues of fetal baboons delivered at 125, 140, and 175 days of gestation (dGA; term=185+/-2 days) and preterm baboons that became naturally infected with bacterial/fungal pathogens. The TLR-mRNA and protein were quantified by Northern and Western blotting, respectively. The expression of both TLRs was significantly low at 125 and 140dGA. At 175dGA, the levels reached equivalent to those in adult baboons. However, in naturally infected baboons, the TLR4-mRNA was reduced (p<0.05); TLR2-mRNA expression remained unaltered. The protein expression of both TLRs was found increased in naturally infected baboons. Our results suggest that the lung TLR expression is developmentally regulated and altered during respiratory infection in preterm babies.