Bacterial resistance to commonly used antibiotics is monitored for a long time by researchers around the world. To estimate the resistance variation to 3(rd) generation Cephalosporin antibiotics, total 1457 strains of the Enterobacteriaceae family (Escherichia coli, Enterobacter aerogenes, Klebsiella pneumonia) were isolated from hospital sewage water. Resistance rates were determined against CRO, ZOX and CTX within two different periods in different water temperature by using disc diffusion technique. The average resistance rates of the isolates to the antibiotics (CRO, ZOX & CTX) in the June- October 2007 were higher than that of the October, 2007-February, 2008. The highest resistance was detected to the ZOX and the lowest one was to the CRO in both periods. K pneumonia showed the highest resistance to all three antibiotics compared to the E. aerogenes and E coli. After plasmid curing, K. pneumonia has lost resistance at the highest level (52.72% to CRO, 44.72% to ZOX, 68.72% to CTX) compared to E coli and E aerogenes.