A new approach to texture classification for quantitative ultrasound liver diagnosis using run difference matrix was developed. The run difference matrix comprised the gray level difference along with a distances. From this run difference matrix, we defined several vectors and parameters such as DOD, DGD, DAD vector, SHP, SMO, SMG, LDE, LDEL etc. Each parameter values calculated in fatty, cirrhotic, normal and chronic hepatitic liver images were plotted in a plane and we found that RDM method was more sensitive to small structural changes than the conventional run length method and showed improved classification ability between the diseases.