Local governments have long been ardently pursuing the industrial specialization effect(MAR externalities) and industrial diversification effect(Jacobs externalities). Such a pursuit has resulted in severe distortion of resource allocation and negative effect on sustainability of local economic development. Regarding the effect from both MAR and Jacobs externalities on local economic development existing literature records notable disputes. Therefore, for local economic development, one important issue is which externality(MAR or Jacobs) can better bring the effect into play. By studying a panel data of 283 Chinese cities from 2003 to 2012 and applying dynamic plane data GMM method, this paper conducted a regression analysis of the relationship among industrial agglomeration externalities, city size, and regional economic development. The result indicates that with regard to the whole nation, MAR externalities are conducive to regional economy development whereas Jacobs externalities will, to an extent, restrain regional economic development. As regards eastern, middle, and western regions, MAR externalities are conducive only to the economic development of the eastern region; their effects on middle and western regions are insignificant. Moreover, the interaction item between MAR externalities and city size has a significant negative synergistic effect on national economic development and a certain acceleration effect on eastern region as well as a strong negative synergistic effect on the middle region and an insignificant effect on the western region. The interaction item between Jacobs externalities and city size has a positive synergistic effect on only the middle region and has an insignificant synergistic effect on both eastern and western regions. Capital stock and labor input have significant accelerating effects on GDP growth per capita of Chinese cities, whereas material capital and labor input remain primary driving forces for Chinese local economic development. Furthermore, human capital contributes to accelerating urban economic development, whereas government intervention restrains urban economic development. Local aseps have long been ardently pursuing the industrial specialization effect (MAR externalities) and industrial diversification effect (Jacobs externalities). Such a seek has resulted in severe distortion of resource allocation and negative effect on sustainability of local economic development. Regarding the effect from both MAR, and Jacobs externalities on local economic development existing literature records notable disputes. Therefore, for local economic development, one important issue is which externality (MAR or Jacobs) can better bring the effect into play. By studying a panel data of 283 Chinese cities from 2003 to 2012 and applying dynamic plane data GMM method, this paper conducted a regression analysis of the relationship among industrial agglomeration externalities, city size, and regional economic development. The result indicates that with regard to the whole nation, MAR externalities are conducive to regional economy development compared Jacobs externalities w ill, to an extent, restrain regional economic development. As regards eastern, middle, and western regions, MAR externalities are conducive only to the economic development of the eastern region; their effects on middle and western regions are insignificant. Moreover, the interaction item between MAR externalities and city size has a significant negative synergistic effect on the middle region and an insignificant effect on the western region. The interaction item between Jacobs externalities and city size has a positive synergistic effect on only the middle region and has an insignificant synergistic effect on both eastern and western regions. Capital stock and labor input have both significant accelerating effects on GDP growth per capita of Chinese cities, while material capital and labor input remain primary driving forces for Chinese local economic development. Moreover, human capital contributes to accelerating urban economic development, while government intervention restrains urban economic development.