Abstract: 【Objective】 This study aimed to analyze the inheritance patterns of major gene+polygene affecting flesh thickness in oriental melons， so as to provide a reference for genetic improvement and breeding of high-quality melon varieties with thick flesh and thin skin. 【Method】 M125 and M30， the advanced inbred lines of oriental melons with obviously different flesh thickness， were taken as parental lines to establish six generations， P₁， P₂， F₁， F₂， B₁， and B₂ for measurement of flesh thickness. The genetic analysis method of major gene+polygene for plant quantitative traits was used to investigate the inheritance patterns of flesh thickness across six generations from 2021 to 2023. 【Result】 From 2021 to 2023，the average flesh thickness of F₁ generation lines was consistently intermediate between the two parental lines. Obvious variations of flesh thickness of oriental melon were observed across F₂， B₁， and B₂ populations， and their coefficients of variation were 25.72%-27.50%，26.10%-34.37%， and 20.11%-24.39%，respectively； the frequency distribution of flesh thickness in the F₂ populations showed continuous variations，indicating that this trait was consistent with the inheritance characteristics of major gene+polygene for quantitative traits. Based on Akaike information criterion （AIC），MX2-A-AD was ultimately selected as the optimal genetic model for flesh thickness from 2021 to 2023， indicating that the flesh thickness of oriental melons was controlled by two pairs of additive main genes+additive-dominant polygenes. The first-order genetic parameter analysis revealed that the additive effects of the first pair of major genes in 2021 was slightly higher than that of the second pair，and in 2022 and 2023，the additive effects of the first pair was lower than that of the second pair. No dominant or interaction effects were observed in major genes in any of the three years，and the additive effects of polygenes exceeded their dominant effects. The second-order genetic parameter analysis revealed that from 2021 to 2023， the major genes controlling flesh thickness exhibited high heritabilities in F₂ populations， the heritabilities of the major genes in F₂ population were 66.46%，67.83%， and 63.68%， and the heritabilities of the polygenes in F₂ population were 4.58%，15.58%， and 0. Apart from the B₁ generation in 2023，all other populations showed higher heritability of major genes than polygenes，indicating that the flesh thickness of oriental melons was primarily determined by major genes. 【Conclusion】 The inheritance of flesh thickness in oriental melons is characterized as a quantitative trait controlled by two pairs of major genes with polygenic modification. The directional selection of the flesh thickness of oriental melon should be practiced in the early generations.