This study was conducted during the period from 2015 to 2017 to study resistance of powdery mildew in eight melon inbred lines and their hybrids in order to reduce losses in quality and yield.  Eight different genetically inbred lines of melon were selfed for six generations to ensure homozygosity. They have been self-pollinated and intercrossed in a half diallel mating design to obtain 28 melon hybrids in 2015. Thirty six melon genotypes (8 inbred Lines and 28 produced hybrids) were evaluated for their reaction to powdery mildew in 2016. The results showed that P5, P6, P7 and P8  of inbred lines, and all hybrids that contain P6 [(P1) X(P6), (P2) X(P6), (P3) X(P6), (P4) X(P6), (P5) X(P6), (P6) X(P7) and (P6) X(P8)]  beside P5X P7, P5X P8 and P7X P8 showed low infection (between 1-12.5%) that is meaning they are resistant. The genetic study showed that most hybrids appeared significant negative heterosis over its mid parent. On the contrary, most studied hybrids appeared significant positive heterosis over its better parent. The most potence ratio estimates indicated dominance towards powdery mildew resistance. In 2017 at WADY El-Natroon, The 36 hybrids were evaluated along with their parents to determine heterosis  and potence ratio for the economic traits, viz., days to picking, early yield/plant, total yield/plant, average fruit weight, fruit shape index, netting, total soluble solids and flesh thickness. The results showed highly significant mean squares for all of the studied traits. Some crosses revealed highly significant and significant mid-parent and better-parent heterosis for many of studied traits. The inbred lines P5, P6 and P7 were resistant to powdery mildew and had good horticultural characteristics. They were the best and promising inbred lines.