This study aimed to investigate the effect of the miR-29c/PTEN axis on the PI3 K/Akt/NF-kB pathway in rats with severe pneumonia (SP). A total of 20 Sprague-Dawley rats were selected, of which 10 were randomly selected for modeling SP and included in the model group (MG) and the other 10 were included in the control group (CG). Expression levels of miR-29c and PTEN were measured in the peripheral blood and lung tissue. Pearson correlation coefficient analysis showed that miR-29c was positively correlated with PTEN in serum and lung tissue (r = 0.833 and 0.697, respectively; P < 0.05). The apoptosis rate was higher in the MG than in the CG (P < 0.05). Western blot analysis revealed that the relative expressions of PI3 K, Akt, and NF-kB proteins were higher in the MG than in the CG (P < 0.05). Protein expression in the miR-29c-mimics and sh-PTEN groups was higher than that in the other two groups, whereas the miR-29c-inhibitor group had the lowest protein expression (P < 0.05). MiR-29c/PTEN exhibited low expression levels in SP, which can promote pneumonia development by inhibiting the expression of PI3 K/Akt/NF-kB pathway proteins.