Abstract: OBJECTIVE To investigate the effect of cinnamaldehyde (CA) on Streptococcus pneumoniae (SP)-induced alveolar epithelial cell injury and apoptosis by modulating the peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) pathway. METHODS Human alveolar epithelial type Ⅱ cells (AT Ⅱ) were cultured and divided into control (Con) group, model (SP) group, low-, medium-, and high-dose CA (L-, M-, H-CA) groups and H-CA + PPARγ inhibitor T0070907 (H-CA+T0070907) group. Cell Counting Kit-8 (CCK-8) and propidium iodide single staining were applied to assess cell proliferation and cycle changes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry were employed to detect apoptosis. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect inflammatory factors. Colorimetric assays and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probes were employed to evaluate oxidative stress indicators. Western blotting was performed to detect protein expression. RESULTS Compared with the Con group, the SP group exhibited decreased cell proliferation viability, S-phase, G2/M-phase, interleukin (IL)-10, superoxide dismutase (SOD), cyclin D1, cyclin-dependent kinase 2 (CDK2), B-cell lymphoma-2 (Bcl-2) and PPARγ, and increased G0/G1-phase, apoptosis rate, IL-6, tumor necrosis factor-α (TNF-α), IL-1β, lactate dehydrogenase (LDH), reactive oxygen species (ROS), Bcl-2-associated X protein (Bax), cleaved caspase-3 and phosphorylated (p)-NF-κB p65/NF-κB p65 (P<0.05). The L-, M-, H-CA group showed opposite trends in these indicators compared to the SP group. The H-CA+T0070907 group exhibited reversed trends compared to the H-CA group. CONCLUSIONS CA can alleviate SP-induced AT Ⅱ cell injury and apoptosis by activating the PPARγ/NF-κB pathway.