CHEVY CHASE, Md. — The unexpected retirement of Senator Barbara Mikulski, the tough-talking Maryland Democrat and longest-serving woman in the history of the Senate, has set off a political frenzy among ambitious Democrats positioning themselves for promotions in this traditionally blue state.

On Tuesday, Representative Donna Edwards became the second Democrat — after Representative Chris Van Hollen, whose district includes this wealthy suburb of Washington — to jump in the race to succeed Ms. Mikulski, setting up what is expected to become a competitive primary in a state where an open Senate seat is a rarity.

Ms. Edwards, who is spotlighting her biography as a single mother and community activist, is casting herself as the progressive. Mr. Van Hollen, the House Budget Committee chairman, has the backing of Harry Reid, the Senate minority leader.

But they may soon have company. The list of those thinking of running is long — and growing longer.

“It’s easier to say who is definitely not running than who is,” said former Gov. Parris Glendening, a Democrat who described the state of play in Maryland as “a major chess game, where everyone is moving around and thinking, ‘I’ll go here, and you’ll go there.’ ”