Results: The results indicated that serum CEA, ALP or CK levels were significantly increased in male and female waterpipe smoking animals (P<0.01, P<0.01 or P<0.001, respectively). There was not gender effect on serum CEA, ALP or CK levels. There were also histological changes in intestinal tissue including increased tissue plasma cells infiltration and inflammation. Conclusion: Our findings show that waterpipe smoking is an enhancer factor of serum CEA, alkaline phosphatase or creatine kinase levels, according to which, damaging effects of waterpipe smoking on various tissues, particularly intestine should be considered seriously.