Abstract : Cigarette smoking has been associated with increases in inflammatory and oxidative stress in tear films and causes decreasing in tear film parameters value and goblet cell density. This study purposed to investigate the effect of acute cigarette smoke exposure on cytokine levels (IL-1, IL-6, and IL-8) and malondialdehyde levels in murine lacrimal gland tissue. The design was posttest-only with a control group study. Thirty-six male Wistar rats, aged three months old with weighing 250-300 grams, were included and divided into two groups, cigarette smoke exposure and the control group. The exposure to cigarette smoke was carried out thrice a day, 30 minutes each, for 21 days. On the 22nd day, the exoorbital lacrimal gland tissues were obtained to examine the concentrations of IL-1, IL-6, and IL-8 with the ELISA test and malondialdehyde levels with the TBARS assay method. The results show significantly elevated cytokines level in the cigarette smoke group, especially IL-1 and IL-8 concentration than the control group. The malondialdehyde levels also increased significant statistically in the cigarette smoke group. Increasing levels of cytokines and malondialdehyde indicate that cigarette smoke exposure promotes the inflammation process and oxidative stress in lacrimal gland tissue. The oxidative stress-induced inflammation process will damage the lacrimal gland, which causes aqueous production disturbance, and eventually causes dry eye disease.