Fredrik Reinfeldt, the Swedish prime minister, announced Arkelsten's resignation on Friday.
"We have come to an agreement for Arkelsten to resign as party secretary," he said.
Arkelsten's resignation comes shortly after she reinstated the Moderates' intention to back legislation requiring party donations over $US 2800 to be publicly declared, as Radio Sweden reported on Thursday.
On Friday, Arkelsten would not elaborate on the reasons she is leaving the position.
"It has been a very fun job. I am proud of what we have achieved so far. I have my reasons and will get back to political plans. I have made my decision and need a change," Arkelsten told news agency TT.
Arkelsten held her post from October 2010 when she replaced Per Schlingmann.
The appointment of Persson, until now a county politician, is thought to bring expertise in local politics to the top level of the Moderate party ahead of the 2014 election.
"We need to work smarter. We also need to work closer to people across the country," Fredrik Reinfeldt continued.
As a county politician, Persson sought to develop the Moderates' welfare policies.
According to PJ Anders Linder, political editor at Swedish daily newspaper Svenska Dagbladet, his work has been well aligned with policies prioritised by Reinfeldt and Anders Borg, the Moderate finance minister.
"He is the clearest spokesperson for the New Moderates project. He is well in line with the profile that Reinfeldt and Borg have been advocating," PJ Anders Linder told Swedish Radio.