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Lake Tana is the largest fresh water lake in Ethiopia affected by anthropogenic activities. This study was designed to assess human impacts on water quality of Lake Tana using some physicochemical parameters. The study was taken in five study areas and 11 sampling sites. The sites were selected based on the impact levels to compare with the reference site as a control based on the international standard selection criteria, APHA (American Public Health Association). The analytical results parameters selected in the study area indicated were Temperature (To) (21.93OC), pH (7.310), EC (electrical conductivity) (157.0µS/cm), BOD5 (biological oxygen demand) (22.30mg/l), COD (chemical oxygen demand) (311.2mg/l), TSS (total suspended solids) (0.5mg/l) and TDS (total dissolved solids) (78.6mg/l). The values of the analyzed parameters showed significant variation among the wet and dry seasons than among different locations (P<0.05). Strong positive correlations are observed between Temperature with EC and BOD5, EC with BOD, COD and TDS, BOD with COD and TDS at the p<0.01. Therefore, the lake water was very poor and unfit for drinking due to human induced pollution and it requires treatment before use.