Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, is one of the major causes of septic shock. Herein we investigate LPS-induced apoptosis of rat alveolar epithelial type II cells (AEC II) and the effects of LPS on surfactant protein-C (SP-C) expression in AEC II, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of AEC II significantly in concentration-dependent manner embodied in increased caspase-3 expression and the activity of caspase-3. Simultaneously, our results also indicated that LPS inhibited surfactant protein-C (SP-C) expression in AEC II. Mechanistic studies revealed that LPS treatment significantly increased the expression of NF-κB p50, NF-κB p65 and IKKβ proteins as well as induced IκB-α phosphorylation. Moreover, pretreatment with IKK inhibitor IKK-16 or NF-κB inhibitor PDTC ameliorated LPS-caused alterations in cleaved caspase-3 expression, the activity of caspase-3 and SP-C expression. Taken together, these results demonstrate that LPS can induce apoptosis of AEC II and decrease SP-C expression partly through activating the NF-κB pathway.