Cholelithiasis is known to produce diverse histopathological changes in the gallbladder mucosa. Objectives: To observe the morphological changes in the gall bladder mucosa associated with cholelithiasis. Study Design: Descriptive Cross Sectional study. Setting: Department of Anatomy, Jamshoro with collaboration of Department of Pathology, LUMHS, Jamshoro. Period: April 2016 to October 2016. Material and Methods: All the cases after diagnosis of cholelithiasis with all age groups (20 to 50 years) in male and female were included. Gallstones were assessed for various parameters, i.e., number, size, and morphological type. Gallbladder mucosa was subjected to histopathological examination. Sections of the body, the fundus and the bottom of the gallbladder were drawn. 01 cm of the body, the body, and the bottom of the gallbladder were drawn from the funduse and prepared for histological research. Data was statistically analyzed by SPSS (Statistical Package of Social Sciences) version 22.0. Results: Total 87 cases were selected and average age of 49.95±6.14 years of male was seen in a gall bladder width and length in the gallbladder and gallbladder length in both sex of P-value 0.07 while male of female average were 41.30añ6.62, age range from 30 to 52 years. Sixty-seven (77.0%) cases had multiple stones. 29 (33.3 percent) patients had congested the serological layer, while 58 (66.7 percent) were usually impacted. Mucosa hemorrhagic in 22(25.3%) cases, atrophic in 51(58.6%) cases and nodular in 4(4.6%) cases. 36(41.4%) gall bladders reported normal results, 41(47.1%), 1(1.1%), and 3(3.4%) were identified with Fibrosis, and 2(2.3%) are found with Fibrosis. Many cases were linked to fibrosis, dysplasia, and hyperplasia, compared to single calculus (P value 0.048). There was no substantial difference between normal and thickened gall bladders in the microscopic tests (P value 0.26). Fibrosis, dysprasia and hyperplasia are correlated mainly with internal mucus detections (P value 0.002). Hemorrhagic mucous membranes are found mainly. Conclusion: Hemorrhagic and fibrotic changes were the most common mucosal findings, and significantly associated with multiple cholelithiasis.