The aim of this study was to investigate the protective effect of Calendula officinalis L. (CO) on rats exposed to cigarette smoke (CS). For this purpose twenty one albino male Sprague Dawley rats were randomly divided into three groups as control, CS and CS+CO. The rats of the CS and CS+CO groups were subjected to CS during 1 h twice a day for 23 days. CO (100 mg/kg body weight) was given to the rats of the CS+CO group by oral gavage one hour before each administration period. Protective effect of CO was detected by comparing some serum biochemical parameters and mean body weight changes of groups. While aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phosphokinase (CK) levels of CS group increased, amylase and lipase decreased significantly compared to control. AST, LDH and CK levels reversed to nearly their control group values by CO supplementation. There was a significant reduction in the HDL level of the CS group compared to control. But its level increased markedly in the CS+CO group. With regard to calcium, its amount escalated significantly in the CS and CS+CO groups compared with control. Administration of CO caused an amendment in the body weight loss. In conclusion, this study revealed that CO could relatively combat the hazardous effects of CS and thus may help to reduce development risk of some disorders related to CS.