Freshwater ecosystems provide various services to many people worldwide. However, degradation of freshwater ecosystems and loss of their services have become pervasive environmental issue across Ethiopia due to ever intensifying human activities, lack of awareness and logistic constraints. As a result, there is an urgent call to develop conservation, management, restoration guidelines, and detail scientific information. To this end, understanding how freshwater biodiversity responding to different human activities is indispensable. Therefore, the purpose of this study was to investigate benthic macroinvertebrate structure in relation to land use types. Benthic macroinvertebrates and physicochemical parameters of water were recorded from 39 sampling sites along Infranz River that represents different human land use activities such as low (n=12), moderate (n=14) and high (n=13) during dry season. The total of 1052 macroinvertebrates belong to 55 families was collected. Macroinvertebrate metrics such as, biological monitoring working party, Shannon diversity index, Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness, total family richness, and average scoring per taxa were decreased with increasing human land use activity: whereas, family biotic index increased with increasing human disturbances. Stepwise regression analysis showed that farming, cattle grazing, and vegetation removal were important predicators of macroinvertebrate metrics (p<0.05). Generally, high values of electrical conductivity, turbidity, total suspended solids, total dissolved solid, and ammonia were record in sites which are characterized by high human disturbance. Keywords: Land use, Benthic macroinvertebrate, Assemblages, Family richness