2010 Regional League Division 2 North-East Region is the 2nd season of the League competition since its establishment in 2009. It is in the third tier of the Thai football league system.
The league was expanded from 12 clubs in 2009 to 16 clubs this season. The league winners and runners up qualified for the 2010 Regional League Division 2 championship stage.
Mukdahan-Savannakhet renamed Mukdahan
Ubon Tiger, Nong Khai, Yasothon United, Nong Bua Lamphu and Kalasin joined the newly expanded league setup.
Ubon United are in the first year of their two-year ban.