Cholelithiasis is one of the most prevalent diseases in gastroenterology, and it is a major public health problem in all developed countries. It has the most common in patient diagnosis among gastrointestinal and liver diseases and it accounts for many hospital admissions and surgical interventions in our local population. Gallstone  disease also known to cause  liver disease and defragment of its enzymes. Our main objective in the this study was to investigate   the biochemical changes in serum liver enzyme and total bilirubin associated with Cholelithiasis. High incidence of cholelithiasis was more prominent among females 127(84.7%) relatives to males 23(15.3%), giving males to females ratio (1:5.5).The most affected age groups were 41-50 years .The majority of patients 62(41.33%) were obese and their body mass index (BMI) 25-30. The most common type of stones was Mixed stones (MS). Serum liver enzymes level of patients was found to be nearly within the same range, whereas their serum total bilirubin significantly increased in comparison with the control group. Furthermore, it is found that there was significant difference between males and females in ALT and AST in patients group. The serum total bilirubin of the patients with pigment stones was significantly elevated. Cholelithiasis is an important cause to significant pathological changes in serum total bilirubin   and slight changes in liver enzymes.